Abstract
Background Circular RNA (circRNA) is a noncoding RNA that forms a closed-loop structure, and its abnormal expression may cause disease. We aimed to find potential network for circRNA-related competitive endogenous RNA (ceRNA) in atrial fibrillation (AF). Methods The circRNA, miRNA, and mRNA expression profiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified, followed by the establishment of DEcircRNA-DEmiRNA-DEmRNA regulatory network. Functional annotation analysis of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. In vitro experiment and electronic validation were used to validate the expression of DEcircRNAs, DEmiRNAs, and DEmRNAs. Results A total of 1611 DEcircRNAs, 51 DEmiRNAs, and 1250 DEmRNAs were identified in AF. The DEcircRNA-DEmiRNA-DEmRNA network contained 62 circRNAs, 14 miRNAs, and 728 mRNAs. Among which, two ceRNA regulatory pairs of hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 were identified. In addition, six miRNA-mRNA regulatory pairs including hsa-miR-34c-5p-INMT, hsa-miR-1253-DDIT4L, hsa-miR-508-5p-SMOC2, hsa-miR-943-ACTA1, hsa-miR-338-3p-WIPI1, and hsa-miR-199a-3p-RAP1GAP2 were also obtained. MTOR was a significantly enriched signaling pathway of host gene of DEcircRNAs. In addition, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcircRNA-DEmiRNA-DEmRNA regulatory network. The expression validation of hsa-circRNA-402565, hsa-miR-34c-5p, hsa-miR-188-5p, SPON1, DDIT4L, SMOC2, and WIPI1 was consistent with the integrated analysis. Conclusion We speculated that hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 interaction pairs may be involved in AF.
Highlights
Atrial fibrillation (AF) is one of the most common arrhythmias and associated with heart failure [1,2,3,4]
We selected data according to the following criteria: (1) the selected dataset must be genome-wide circRNA/miRNA/mRNA transcriptome data; (2) these data were obtained from the heart tissues of the patients in the atrial fibrillation (AF) group and the normal control (NC) group; (3) standardized or original datasets were considered in this study
We found several DEmiRNADEmRNA regulatory pairs such as hsamiR-34c-5p-indolethylamine N-methyltransferase (INMT), hsa-miR-1253-DNA damage-inducible transcript 4 like (DDIT4L), hsa-miR-508-5p-SPARC-related modular calcium binding 2 (SMOC2), hsa-miR-943-actin alpha 1, skeletal muscle (ACTA1), hsa-miR-338-3p-WD repeat domain, phosphoinositide-interacting 1 (WIPI1), and DEmiRNA-differentially expressed mRNAs (DEmRNAs) regulatory pair including hsa-miR-199a-3p-RAP1 GTPase-activating protein 2 (RAP1GAP2)
Summary
Atrial fibrillation (AF) is one of the most common arrhythmias and associated with heart failure [1,2,3,4]. The circRNA, miRNA, and mRNA expression profiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively. Expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified, followed by the establishment of DEcircRNA-DEmiRNA-DEmRNA regulatory network. Functional annotation analysis of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. The DEcircRNA-DEmiRNA-DEmRNA network contained 62 circRNAs, 14 miRNAs, and 728 mRNAs. Among which, two ceRNA regulatory pairs of hsa-circRNA-100053-hsamiR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 were identified. MTOR was a significantly enriched signaling pathway of host gene of DEcircRNAs. In addition, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcircRNA-DEmiRNADEmRNA regulatory network. The expression validation of hsa-circRNA-402565, hsa-miR-34c-5p, hsa-miR-188-5p, SPON1, DDIT4L, SMOC2, and WIPI1 was consistent with the integrated analysis. We speculated that hsa-circRNA-100053hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 interaction pairs may be involved in AF
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